Prions are classically understood as infectious agents capable of transmission by a mechanism of conformational templating where native protein is converted to the prion form and as such, unlike any other transmissible agent, does not involve nucleic acid. Prions however also influence a range of cellular phenotypes in yeast and beyond without any resulting detriment to the host so can act as functional epigenetic determinants of phenotype and perhaps even drivers of evolution. The prion form of the eukaryotic release factor Sup35p forms the [Pst] prion which amongst other effects, leads to adoption of a nonsense suppression phenotype. The as yet poorly understood entity responsible for maintaining the [Pst] phenotype in a dividing population has been termed the propagon. Although [Pst] is attributable to prionised Sup35p material, which assembles into high molecular weight amyloid like structures, no specific structural species has been specifically credited with propagon activity. The following work describes optimised methods for use in characterising key properties of the [Pst] system relating to propagation, and applies them along with novel new approaches to investigate the molecular nature of the propagon. Prion systems may be capable of adapting cell populations to changes in environment however how this is achieved is unclear. Propagon function as a modulator of phenotype was investigated in response to glucose exhaustion, key changes to the prion system were observed and characterised and the ro le of prions systems in cell ular responses to environment discussed. Size appears to be a defining property of aggregate transmissibility however how size influences propagon activity beyond affecting diffusion properties is unclear. Organisation of low molecular weight species into high molecular weight aggregates provides a clear determinant of size however very little is understood about the nature or significance of such organisation. The fo llowing work explores the molecular nature and biological relevance of these two species and discusses how they may influence our understanding of the [PSI] system.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:594230 |
| Date | January 2011 |
| Creators | Naeimi, Wesley Reza |
| Publisher | University of Kent |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
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